Current approaches for the delivery of drug to the upper urinary tract, such as to treat upper urinary tract infections (UTIs), upper tract urothelial carcinoma (UTUC), and related complications, are unsatisfactory. For example, topical urinary tract instillation has been used to treat UTUC; however, such instillations suffer the drawback of providing only a relatively short and insufficient duration of drug exposure, or dwell time (Audenet et al., “Upper Urinary Tract Instillations in the Treatment of Urothelial Carcinomas: A Review of Technical Constraints and Outcome” World J. Urol. 31(1):45-52 (February 2013)). UTIs are currently treated using systemic (e.g., oral) antibiotic therapy, requiring large doses of drug for multiple days or weeks, which undesirably increases the risk of side effects including nephrotoxicity and/or the development of a superinfection and drug resistance.
Efforts have been proposed to improve drug instillation dwell times in the treatment of UTUC by instilling the drugs with hydrogel polymers having reverse thermal gelation properties (liquid state at cold temperatures and solid state at body temperature). However, these hydrogel polymers have been found to still have relatively short retention potential and therefore, similar to conventional instillation treatments, are believed to be incapable of delivering drug to a treatment area for a sufficient period (e.g., more than a day) to provide a therapeutic effect.
Ureteral drug delivery stents are known. For example, some ureteral stents have been made of a drug-impregnated polymer. However, drug release from such matrix material release systems has been generally unsatisfactory due to the relatively low drug payload that such systems are able to contain and deliver. Furthermore, release of drug is limited by diffusion from and/or degradation of the polymer matrix, which limits the drug release rates that can be achieved. Mechanical requirements of the matrix-drug composition further limit the total amount of drug payload that can devices can contain.
Another ureteral stent-type device is disclosed in U.S. Pat. No. 9,259,517. The device requires a balloon portion, which resides within the bladder and which must be filled with a drug solution after the device is deployed in the bladder. This feature unfortunately complicates the process of using the device. It also requires an undesirably large and potentially intolerable (or at least highly uncomfortable, to the patient) drug reservoir reside in the bladder during the period of drug release, due to the large volume needed for the inflated balloon to contain both the drug and all of the liquid vehicle needed for releasing the drug.
It therefore would be desirable to provide new and improved methods and devices for controlled delivery of drug to the renal pelvis area in effective amounts for extended periods. It would be desirable for such drug delivery devices and methods to be easily inserted into and removed from a patient's ureter, preferably without requiring an additional step to load a liquid vehicle into (or remove the liquid vehicle from) the device's drug reservoir after the device has been inserted into the patient's bladder.